GENETIC POLYMORPHISM OF F2, F5 AND VKORC1 IN POPULATIONS OF BURYATS, TELEUTS AND RUSSIANS OF THE EASTERN SIBERIA

DOI: https://doi.org/10.29296/24999490-2018-03-06

L.E. Tabikhanova(1), L.P. Osipova(1, 3), T.V. Churkina(1), E.N. Voronina(2, 3), M.L. Filipenko(2, 3) 1-The Federal Research Center Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, Prospekt Lavrentyeva, 10, Novosibirsk, Russian Federation, 630090; 2-Institute of Chemical Biology and Fundamental Medicine, the Siberian Branch of the Russian Academy of Sciences, Prospekt Lavrentyeva, 8, Novosibirsk, Russian Federation, 630090; 3-Novosibirsk State University, Pirogova str., 2, Novosibirsk, Russian Federation, 630090 E-mail: [email protected]

Introduction. The study of the prevalence of genetic risk factors for thrombosis-associated diseases in the indigenous population of Siberia is an important issue in current medicine. The aim of the study. The aim of this work is to study the allele frequencies of the clotting factor genes F2 (G20210A, rs1799963) and F5 (G1691A Leiden, rs6025) and the VKORC1 gene (C1173T, rs9934438) in the Teleut population, the Buryat population and their Métises in comparison with the Eastern Russian populations. Methods. The Real-time polymerase chain reaction with competitive TaqMan allele-specific probes. Results. The mutation F5 (1691A, Leiden) was not detected in cohorts of Buryat, Teleut and Buryat Métis, its prevalence accounted for 1,3% among Russians. The mutation F2 (20210A) was not found in Teleuts and Buryat Métis, it was detected with a low frequency of 0.1% in the total cohort of the Buryat. The frequency of this mutation in the Russians of East Siberia is 1.3%. The occurrence of the VKORC1 (1173T) allele in two of the Buryat populations (88,9% and 87,1%) and Teleuts (74,6%) is significantly higher than in the Russians of East Siberia (43,6%). The frequency of variant 1173T of the gene VKORC1 in the progeny of mixed marriages of Buryats with Russians is 68,2%.Conclusion. The obtained data makes it possible to predict a reduced risk of thrombosis-associated diseases among Teleuts and Buryats. However, one should consider the risk of overdose of indirect anticoagulants in the treatment of members of these ethnic groups
Keywords: 
F2 (G20210A, rs1799963), F5 (G1691A, rs6025, Leiden), VKORC1 (С1173T, rs9934438), Buryats, Teleuts, Russians of Eastern Siberia

Список литературы: 
  1. Rosendaal F.R., Doggen C.J., Zivelin A., Arruda V.R., Aiach M., Siscovick D.S., Hillarp A., Watzke H.H., Bernardi F., Cumming A.M., Preston F.E., Reitsma P.H. Geographic distribution of the 20210 G to A prothrombin variant. Thromb Haemost. 1998; 79 (4): 706–8. http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.912.238&rep=rep1&type=pdf
  2. Bogdanov I.G., Bogdanova A.S., Miromanova N.A., Strambovskaya N.N., Dimova S.N., Vitkovskiy Yu.A. Rasprostranennost` mutacii faktora VA (Leyden) na territorii Zabaykal`ya. Dal`nevostochnyy medicinskiy zhurnal. 2007; 1: 33–4. http://elibrary.ru/download/elibrary_21119737_12555367.pdf [Bogdanov I.G., Bogdanova A.S., Miromanova N.A., Strambovskaya N.N., Dimova S.N., Vitkovsky Y.A. Frequency of Leiden mutation among healthy residents of Transbaikalia. Dal’nevostochnyy meditsinskiy zhurnal. 2007; 1: 33–4 (in Russian)]
  3. he 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012; 491 (7422): 56–65. doi: 10.1038/nature11632. www.1000genomes.org https://www.nature.com/nature/journal/v491/n7422/pdf/nature11632.pdf
  4. Korchagina R.P., Osipova L.P., Vavilova N.A., Voronina E.N., Filipenko M.L. Polimorfizm gena VKORC1 (1173T), opredelyayushhego chuvstvitel`nost` individov k varfarinu, v populyaciyah korennyh e`tnosov sel`kupov i tundrovyh nencev, a takzhe russkih Severnoy Sibiri. Vestnik Kemerovskogo gosudarstvennogo universiteta. 2012; 1 (49): 19–23. http://elibrary.ru/download/elibrary_17682801_41141793.pdf [Korchagina R. P., Osipova L. P., Vavilova N. A., Voronina E. N., Filipenko M. L. The polymorphism of the VKORC1 (1173T) gene, determining individual susceptibility to warfarin, in populations of indigenous peoples of Selkups and Tundra Nenets and in the Russians of Northern Siberia. Vestnik Kemerovskogo gosudarstvennogo universiteta. 2012; 1 (49): 19–23 (in Russian)]
  5. Ivashchenko D., Rusin I., Sychev D., Grachev A. The frequency of CYP2C9, VKORC1, and CYP4F2 polymorphisms in Russian patients with high thrombotic risk. Medicina (Kaunas). 2013; 49 (12): 517–21. https://www.ncbi.nlm.nih.gov/pubmed/24858991
  6. Chertovskikh Y.V., Malova E.U., Maksimova N.R., Popova N.V., Sychev D.A. VKORC1 polymorphisms and warfarin maintenance dose in population of Sakha (Yakuts). International Journal of Risk and Safety Medicine. 2015; 27 (1): 17–8. doi: 10.3233/JRS-150673. http://content.iospress.com/download/international-journal-of-risk-and-safety-in-medicine/jrs673?id=international-journal-of-risk-and-safety-in-medicine%2Fjrs673
  7. Tiys R.P., Osipova L.P., Tabihanova L.E`., Churkina T.V., Lichman D.V., Voronina E.N., Filipenko M.L. Geneticheskiy polimorfizm faktorov sistemy svertyvaniya krovi FII i FV v populyaciyah korennyh e`tnosov (tundrovyh i lesnyh nencev, nganasan), russkih Severnoy Sibiri i ih metisov v svyazi s riskom razvitiya trombozov. Medicinskaya genetika. 2015; 14 (7): 27–31. [Tiis R.P., Osipova L.P., Tabikhanova L.E., Churkina T.V., Lichman D.V., Voronina E.N., Filipenko M.L. Genetic polymorphism of coagulation system factors FII and FV in populations of native peoples (Tundra Nenets, Forest Nenets, Nganasans), Russians of the North Siberia and their metis in relation to thrombosis risk. Meditsinskaya genetika. 2015; 14 (7): 27–31 (in Russian)]
  8. Shherbak S.G., Kamilova T.A., Lisovec D.G., Sarana A.M., Yurkina E.A., Yurkin A.K., Makarenko S.V., Klenkova N.A., Anisenkova A.Yu., Saharovskaya A.A., Glotov O.S., Glotov A.S., Maksimov A.G. Geneticheskiy polimorfizm sistemy gemostaza (obzor literatury). Vestnik Severo-Zapadnogo gosudarstvennogo medicinskogo universiteta im. I.I. Mechnikova. 2015; 7 (4): 66–75. https://elibrary.ru/download/elibrary_25377719_39683358.pdf [Sherbak S.G., Kamilova T.A., Lisovetch D.G., Sarana A.M., Jurkina E.A., Jurkin A.K., Makarenko S.V., Klenkova N.A., Anisenkova A.J., Saharovskaia A.A., Glotov O.S., Glotov A.S., Maximov A.G. Genetic polymorphism of haemostasis. Vestnik Severo-Zapadnogo gosudarstvennogo meditsinskogo universiteta im. I.I. Mechnikova. 2015; 7 (4): 66–75 (in Russian)]
  9. Dem`yanenko A.V., Kapustin S.I., Soroka V.V., Chechulov P.V. Rol` geneticheskogo polimorfizma komponentov plazmennogo zvena gemostaza v patogeneze venoznogo tromboe`mbolizma (obzor literatury). MEDLINE.RU. 2013; 14 (4): 819–44. http://medline.ru/public/art/tom14/art66.html [Demyanenko A.V., Kapustin S.I., Soroka V.V., Chechulov P.V. Genetic polymorphism of soluble haemostatic factors in the pathogenesis of venous thromboembolism. MEDLINE.RU. 2013; 14 (4): 819–44 (in Russian)]
  10. Miles J.S., Miletich J.P., Goldhaber S.Z., Hennekens C.H., Ridker P.M. G20210A mutation in the prothrombin gene and the risk of recurrent venous thromboembolism. J. Am. Coll. Cardiol. 2001; 37 (1): 215–8. http://www.sciencedirect.com/science/article/pii/S0735109700010809
  11. Rosendaal F.R., Reitsma P.H. Genetics of venous thrombosis. J. Thromb Haemost. 2009; 7 (1): 301–4. doi: 10.1111/j.1538-7836.2009.03394.x. http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2009.03394.x/abstract;jsessionid=D7CC2365B2946C002AE0BF38F0A6D4BF.f03t03
  12. Ye Z., Liu E.H., Higgins J.P., Keavney B.D., Lowe G.D., Collins R., Danesh J. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet. 2006; 367 (9511): 651–8. http://www.sciencedirect.com/science/article/pii/S0140673606682639
  13. Rubanenko A.O., Shhukin Yu.V. Genotip SS gena VKORC1 associiruetsya s aktivaciey kaskada koagulyacii i snizheniem fibrinoliticheskoy aktivnosti u pacientov s fibrillyaciey predserdiy. Prakticheskaya medicina. 2015; 2: 53–5. http://elibrary.ru/download/elibrary_26010076_26389901.pdf [Rubanenko A.O., Schukin Yu.V. VKORC1 CC genotype is associated with activation of the coagulation cascade and reduction of fibrinolytic activity in patients with atrial fibrillation. Prakticheskaya meditsina. 2015; 2: 53–5 (in Russian)]
  14. Wadelius M., Chen L.Y., Downes K., Ghori J., Hunt S., Eriksson N., Wallerman O., Melhus H., Wadelius C., Bentley D., Deloukas P. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J. 2005; 5 (4): 262–70. https://www.nature.com/tpj/journal/v5/n4/full/6500313a.html
  15. D’Andrea G., D’Ambrosio R.L., Di Perna P., Chetta M., Santacroce R., Brancaccio V., Grandone E., Margaglione M. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood. 2005; 105 (2): 645–9. http://www.bloodjournal.org/content/105/2/645.long?sso-checked=true
  16. Zolotareva I.M. Antropologicheskiy tip sovremennyh buryat. Voprosy antropologii. 1960; 5: 98–108. [Zolotareva I.M. Anthropological type of modern Buryats. Voprosy antropologii. 1960; 5: 98–108 (in Russian)]
  17. Tabikhanova, L. E. Osipova, L. P. Analysis of the genetic and demographic structure of populations from Aginskii Buryat district contrasting in habitation conditions. Russian Journal of Genetics. 2012; 48: 1239–46. http://download.springer.com/static/pdf/755/art%253A10.1134%252FS1022795412110129.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1134%2FS1022795412110129&token2=exp=1492177934~acl=%2Fstatic%2Fpdf%2F755%2Fart%25253A10.1134%25252FS1022795412110129.pdf%3ForiginUrl%3Dhttp%253A%252F%252Flink.springer.com%252Farticle%252F10.1134%252FS1022795412110129*~hmac=06cc297b7c2a315f9e30ccd99dcd65244624765b332183673aab3bfc83554c45
  18. Dolgih B.O. Nekotorye dannye k istorii obrazovaniya buryatskogo naroda. Voprosy e`tnogeneza i istoricheskoy e`tnografii. 1953; 1: 38–63. [Dolgikh B.O. Some data on the history of education of the Buryat people. Voprosy etnogeneza i istoricheskoy etnografii. 1953; 1: 38–63 (in Russian)]
  19. Lavryashina M. B., Ul`yanova M. V., Tolochko T. A., Solopekin N. V., Padyukova A. D., Druzhinin V. G. Korennye narody Kemerovskoy oblasti: osobennosti dinamiki demograficheskih processov v populyaciyah teleutov i shorcev (1940–2012 gg.). Vestnik Kemerovskogo gosudarstvennogo universiteta. 2013; 3–2 (55): 13–20. https://elibrary.ru/download/elibrary_20283894_74718758.pdf [Lavryashina M. B., Ulianova M. V., Tolochko T. A., Solopekin N. V., Padyukova A. D., Druzhinin V. G. The indigenous peoples of the Kemerovo oblast: specific dynamics of demographic processes in populations of the Teleuts and the Shors (1940–2012). Vestnik Kemerovskogo gosudarstvennogo universiteta. 2013; 3–2 (55): 13–20 (in Russian)]
  20. Wu O., Robertson L., Langhorne P., Twaddle S., Lowe G.D., Clark P., Greaves M., Walker I.D., Brenkel I., Regan L., Greer I.A. Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thromb Haemost. 2005; 94 (1): 17–25. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0022045/